title: Oxidative stress and apoptosis in a pig model of brain death (BD) and living donation (LD).
abstract: BACKGROUND
  As organ shortage is increasing, the acceptance of marginal donors increases, which might result in poor organ function and patient survival. Mostly, organ damage is caused during brain death (BD), cold ischemic time (CIT) or after reperfusion due to oxidative stress or the induction of apoptosis. The aim of this study was to study a panel of genes involved in oxidative stress and apoptosis and compare these findings with immunohistochemistry from a BD and living donation (LD) pig model and after cold ischemia time (CIT).
  
  
  METHODS
  BD was induced in pigs; after 12 h organ retrieval was performed; heart, liver and kidney tissue specimens were collected in the BD (n = 6) and in a LD model (n = 6). PCR analysis for NFKB1, GSS, SOD2, PPAR-alpha, OXSR1, BAX, BCL2L1, and HSP 70.2 was performed and immunohistochemistry used to show apoptosis and nitrosative stress induced cell damage.
  
  
  RESULTS
  In heart tissue of BD BAX, BCL2L1 and HSP 70.2 increased significantly after CIT. Only SOD2 was over-expressed after CIT in BD liver tissue. In kidney tissue, BCL2L1, NFKB, OXSR1, SOD2 and HSP 70.2 expression was significantly elevated in LD. Immunohistochemistry showed a significant increase in activated Caspase 3 and nitrotyrosine positive cells after CIT in BD in liver and in kidney tissue but not in heart tissue.
  
  
  CONCLUSIONS
  The up-regulation of protective and apoptotic genes seems to be divergent in the different organs in the BD and LD setting; however, immunohistochemistry revealed more apoptotic and nitrotyrosine positive cells in the BD setting in liver and kidney tissue whereas in heart tissue both BD and LD showed an increase.
authors.affiliation: Division of Surgery, Department of Transplantation Surgery, Medical University, Auenbruggerplatz 29, Graz 8036, Austria. philipp.stiegler@medunigraz.at.
authors.forename: Philipp
authors.initials: P
authors.lastname: Stiegler
authors.forename: Michael
authors.initials: M
authors.lastname: Sereinigg
authors.forename: Andreas
authors.initials: A
authors.lastname: Puntschart
authors.forename: Andrea
authors.initials: A
authors.lastname: Bradatsch
authors.forename: Thomas
authors.initials: T
authors.lastname: Seifert-Held
authors.forename: Iris
authors.initials: I
authors.lastname: Wiederstein-Grasser
authors.forename: Bettina
authors.initials: B
authors.lastname: Leber
authors.forename: Elke
authors.initials: E
authors.lastname: Stadelmeyer
authors.forename: Nadia
authors.initials: N
authors.lastname: Dandachi
authors.forename: Siglinde
authors.initials: S
authors.lastname: Zelzer
authors.forename: Florian
authors.initials: F
authors.lastname: Iberer
authors.forename: Vanessa
authors.initials: V
authors.lastname: Stadlbauer
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001926:Brain Death / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics; D016133:Polymerase Chain Reaction; D034421:Sus scrofa
chemical_list: D053148:Caspase 3